Role of Oxidative Stress in Cigarette Smoke Induced Developing Germ Cell Death
Abstracts
Initial Award Abstract |
Cigarette smoke is a known reproductive hazard associated with delayed conception and early menopause. Among the chemicals that are found in tobacco smoke, benzo(a)pyrene (BaP), as a byproduct from the burning of organic materials, is present in high concentrations. BaP is a known ovarian toxicant shown to deplete ovarian egg reserves in rodents. An important determinant of this reserve is the precursor to egg cells that develop in the ovary during gestation, primordial germ cells (PGCs). This developing ovary is especially sensitive to compounds in cigarette smoke, including BaP. It has been previously shown that treating pregnant mice with BaP results in decreased fertility in female offspring due to their ovaries having fewer egg cells. Our past work has shown this to increased cell death of PGCs in the fetal ovary is caused by exposure to BaP. This proposal aims to understand how exposing mouse embryonic ovaries to BaP leads to increased PGC death, thus depleting egg cell reserves of the fetuses. Our study will address this broad question in two ways. The first will be to examine if BaP increases production of harmful reactive oxygen species in the ovary. The second will be to investigate how BaP affects the cells by looking for DNA damage from those reactive oxygen species and signals that induce cell death in the exposed ovaries. Through providing this useful information on how a common chemical found in cigarette smoke induces increased cell death of PGCs, leading to decreased ovarian reserve of egg cells, we can further our understanding of how cigarette smoke exposure is linked to early menopause. |